G-CSF prevents cardiac remodeling after myocardial infarction by activating the Jak-Stat pathway in cardiomyocytes

Nat Med. 2005 Mar;11(3):305-11. doi: 10.1038/nm1199. Epub 2005 Feb 20.


Granulocyte colony-stimulating factor (G-CSF) was reported to induce myocardial regeneration by promoting mobilization of bone marrow stem cells to the injured heart after myocardial infarction, but the precise mechanisms of the beneficial effects of G-CSF are not fully understood. Here we show that G-CSF acts directly on cardiomyocytes and promotes their survival after myocardial infarction. G-CSF receptor was expressed on cardiomyocytes and G-CSF activated the Jak/Stat pathway in cardiomyocytes. The G-CSF treatment did not affect initial infarct size at 3 d but improved cardiac function as early as 1 week after myocardial infarction. Moreover, the beneficial effects of G-CSF on cardiac function were reduced by delayed start of the treatment. G-CSF induced antiapoptotic proteins and inhibited apoptotic death of cardiomyocytes in the infarcted hearts. G-CSF also reduced apoptosis of endothelial cells and increased vascularization in the infarcted hearts, further protecting against ischemic injury. All these effects of G-CSF on infarcted hearts were abolished by overexpression of a dominant-negative mutant Stat3 protein in cardiomyocytes. These results suggest that G-CSF promotes survival of cardiac myocytes and prevents left ventricular remodeling after myocardial infarction through the functional communication between cardiomyocytes and noncardiomyocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • DNA-Binding Proteins / biosynthesis
  • Enzyme Activation
  • Granulocyte Colony-Stimulating Factor / administration & dosage
  • Granulocyte Colony-Stimulating Factor / metabolism
  • Granulocyte Colony-Stimulating Factor / pharmacology*
  • Granulocyte Colony-Stimulating Factor / therapeutic use
  • Hematopoietic Stem Cell Mobilization
  • Janus Kinase 2
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Myocardial Infarction / drug therapy
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / physiopathology*
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / physiology*
  • Protein-Tyrosine Kinases / biosynthesis
  • Proto-Oncogene Proteins / biosynthesis
  • Rats
  • Receptors, Granulocyte Colony-Stimulating Factor / biosynthesis
  • STAT3 Transcription Factor
  • Signal Transduction
  • Time Factors
  • Trans-Activators / biosynthesis
  • Ventricular Function / drug effects
  • Ventricular Remodeling / drug effects*


  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • Receptors, Granulocyte Colony-Stimulating Factor
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Stat3 protein, rat
  • Trans-Activators
  • Granulocyte Colony-Stimulating Factor
  • Protein-Tyrosine Kinases
  • Jak2 protein, mouse
  • Jak2 protein, rat
  • Janus Kinase 2